rs149868979

Positions:

chr16-23380566-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP5_ModerateBP4

The NM_000336.3(SCNN1B):c.1688G>A(p.Arg563Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000861 in 1,614,208 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 1 hom. )

Consequence

SCNN1B
NM_000336.3 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

SCNN1B (HGNC:10600): (sodium channel epithelial 1 subunit beta) Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene encodes the beta subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), and Liddle syndrome. [provided by RefSeq, Apr 2009]

SCNN1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP5

Variant 16-23380566-G-A is Pathogenic according to our data. Variant chr16-23380566-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 561264.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.1114372). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1B	NM_000336.3 linkuse as main transcript	c.1688G>A	p.Arg563Gln	missense_variant	13/13	ENST00000343070.7	NP_000327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7 linkuse as main transcript	c.1688G>A	p.Arg563Gln	missense_variant	13/13	1	NM_000336.3	ENSP00000345751	P1	P51168-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000147

AC:

AN:

251322

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000787

AC:

115

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000603

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000158

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000137

Hom.:

Bravo

AF:

0.000238

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Low renin, low aldosterone hypertension

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

GeneID Lab - Advanced Molecular Diagnostics

Mar 10, 2018

This variant results in an amino acid alteration, replacing an arginine(R) with a glutamine (Q) at position 563, written as p.Arg563Gln or p.Q889H. . in silico prediction algorithms does not provide uniform data regarding the effect of this change on protein structure and function, and it has not been reported in the Clin Var Database (NCBI National Library of Medicine, NIH) but it has been described in 16 alleles out of 121124, in the ExAC database, the majority (9) belonging to heterozygous carries of Latino origin. The variant has been associated with low-renin, low-aldosterone hypertension in South African black and mixed-ancestry individuals, the authors conclude that only a portion of subjects with the R563Q allele fully express the Liddleâ€™s syndrome phenotype (J Hypertens. 2003 May;21(5):921-6). Moreover, there is a positive correlation with pre-eclampsia in this population (BJOG. 2006 May;113(5):595-8). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.;.;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.84

T;T;T;T

M_CAP

Benign

0.079

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.7

L;.;.;.

MutationTaster

Benign

0.74

D;D;D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.64

N;N;N;N

REVEL

Uncertain

0.46

Sift

Benign

0.32

T;T;T;T

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.090

B;.;.;.

Vest4

0.30

MVP

0.82

MPC

0.19

ClinPred

0.032

GERP RS

1.4

Varity_R

0.050

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over